The present invention relates to surface modification, of polymers to act as carriers of radioisotopes and to encapsulation of the radioactive modified surface, for use in radiation therapy devices, for example.
Within this application several publications are referenced by Arabic numerals within parenthesis. Full citations for these and other publications may be found at the end of the specification immediately preceding the claims. The disclosures of all of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
Percutaneous transluminal coronary angioplasty is one of the most common current therapies for symptomatic, obstructive atherosclerotic coronary artery and peripheral arterial disease. Unfortunately, a major limitation remains the restenosis rates as high as 30% to 50% with these procedures (1, 2). The limited impact on restenosis achieved with intracoronary stents is due to a greater early gain, with no reduction in late loss, implying a persistent neointimal proliferative response (3, 4).
Applicant have previously illustrated the ability of intravascular sources of ionizing radiation to prevent neointimal proliferation in models of restenosis. The effects of ionizing radiation on cell proliferation and vascular remodeling were previously demonstrated in several animal studies (5–9) and in early clinical trials (10 –12). A number of platforms have been devised to deliver brachytherapy for catheter-based systems with high-dose rate: Beta—emitters delivered by catheter-based approaches include 90Y wire sources (Schneider), encapsulated 90Sr/Y (Novoste) and 32P seeds (Guidant), and 188Re as a solution source for balloon inflation (13). 192Iridium, a gamma emitter, has been developed in wire-affixed seed geometry (Cordis J&J). For reasons of shielding and patient and operator safety, a clear preference exists for beta sources, although the relative efficacy of various isotopic sources is still under investigation.
Chitin is a cellulose-like biopolymer distributed widely in nature, especially in the crustaceans, insects, fungi and yeast. Its derivative, Chitosan, (1,4)-2-amino-2-deoxy-B-D-glucan, is a natural polymer generally obtained by extensive deacetylation of chitin isolated from crustacean shells. Due to its special biological, chemical and physical properties, chitosan and its derivatives have applications in many industrial, agriculture and biomedical activities as a chelating agent for heavy metal ions (14, 15). Chitosan hydrogels synthesized from chitosan and D, L-lactic acid have been reported in the literature (16, 17). The free amino groups and porous structure of chitosan hydrogels provide them the ability to adsorb o-phosphoric acid (PA) in aqueous solution.
Others have reported forming metallic stents with a Beta emitting source of Rhenium—188 using chelating microfilm having inorganic components (26). However, the prior art does not appear to provide a method of producing an isotope on a polymer layer surface substantially free of inorganic polymers.